Osteoporosis is a major problem in elderly population. We tested the hypothesis whether vascular endothelial growth factor (VEGF-A) gene transfer is an appropriate way to enhance bone formation and recruitment of osteoblasts in vivo. Adenovirus vectors containing VEGF-A or lacZ cDNAs (1.4x10(10) pfu) were injected locally into right distal femurs of New Zealand White rabbits. Saline was injected into all contralateral distal femurs. One and three weeks after the gene transfers femurs were collected for analyses. X-Gal staining showed that up to 20% of the bone marrow cells were transfected although gene transfer also resulted in biodistribution of the vector and expression of the transgene in liver and spleen. Trabecular bone hard tissue histomorphometry of the distal femurs was performed to analyze the effect of gene transfer on bone turnover. When compared with unilateral lacZ transfected trabecular bone at one-week and three-week time points, VEGF-A gene transfer significantly increased bone formation parameters, such as osteoblast number, osteoid volume, and bone volume. Also, bone resorption surface was greatly reduced. It is concluded that injection of adenovirus vector can transfect bone marrow cells in vivo with a relatively high efficiency. Our results suggest that adenovirus-mediated VEGF-A gene transfer induces bone formation via increasing osteoblast activity and may be useful for the treatment of osteoporosis and other diseases that require efficient osteogenic therapy.
Osteoporosis is a growing health problem not only in women but also in men. To assess determinants of bone mineral density (BMD) at the spine and proximal femur, a randomly selected sample of 140 Finnish men aged 54-63 years was measured using fan beam dual-energy X-ray absorptiometry. Isometric muscle strength was measured using a computerized measurement system and cardiorespiratory fitness was assessed with maximal oxygen uptake (VO2 max) using breath-by-breath respiratory gas analyses during an incremental bicycle ergometer exercise. Intakes of calcium and energy were estimated using 4-day food records. Smoking habits and alcohol consumption were assessed from an interview and a 4 week diary, respectively. Isometric muscle strength of triceps and biceps brachii, extensors and flexors of thigh and rectus abdominis correlated significantly with BMD (r = 0.18-0.35, p = 0.02-0.000). Calcium intake correlated positively with femoral (r = 0.19-0.28, p = 0.03-0.003), but not with lumbar BMD. In addition, calcium intake adjusted for dietary energy content (mg/MJ) correlated with femoral BMD (r = 0.25-0.36, p = 0.03-0.000). Smoking had no effect on BMD, whereas alcohol intake correlated positively with BMD at L2-L4 (r=0.19, p = 0.031). In the multiple linear regression analysis adjusted calcium intake predicted BMD in every site measured, while strength of abdominal muscles predicted BMD at Ward's triangle and femoral neck. Body weight was a predictor of trochanteric BMD. Body height was the best predictor of lumbar and femoral neck area. We conclude that low dietary calcium intake, weak muscle strength and low body weight are risk factors for low BMD in men.
The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density (BMD) in middle-aged men. A population based sample of 140 men (53-62 years) was randomly assigned into the exercise and reference groups. BMD and apparent volumetric BMD (BMDvol) of the proximal femur and lumbar spine (dual-energy X-ray absorptiometry, DXA) and anthropomorphic measurements were performed at the randomization and 2 and up to 4 years later. The participation rate was 97% and 94% at the second and third BMD measurements, respectively. As another indication of excellent adherence and compliance, the cardiorespiratory fitness (aerobic threshold) increased by 13% in the exercise group. The 2% decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness. Regardless of the group, there was no association between the increase in aerobic threshold and change in BMD. In the entire group, age-related bone loss was seen in the femoral neck BMD and BMDvol (p < 0.01). BMD and BMDvol values increased with age in L2-L4 (p < 0.004). An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake (p = 0.003). Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck (p = 0.040). A decrease in body height associated with decreased total femoral BMD (r = 0.19, p = 0.04) and the change in body height was a predictor of bone loss in the femoral neck (beta = 0.201). Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD. On the other hand, possible structural alterations, which are also essential for the mechanical strength of bone, can not be detected by the DXA measurements used in this study. The increase seen in lumbar BMD reflects age-related changes in the spine, thus making it an unreliable site for BMD follow-up in men.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.